髓过氧化物酶
炎症
再灌注损伤
缺血
肝损伤
细胞凋亡
肿瘤坏死因子α
药理学
化学
生物
病理
医学
免疫学
内科学
生物化学
作者
Timothy Borjas,Asha Jacob,Molly Kobritz,Vihas Patel,Gene F. Coppa,Monowar Aziz,Haichao Wang
出处
期刊:The journal of trauma and acute care surgery
[Ovid Technologies (Wolters Kluwer)]
日期:2023-02-02
卷期号:94 (5): 702-709
被引量:1
标识
DOI:10.1097/ta.0000000000003877
摘要
INTRODUCTION Extracellular cold-inducible RNA-binding protein (eCIRP) is a novel mediator of inflammation and tissue injury. It has been shown that miRNA 130b-3p acts as an endogenous inhibitor of eCIRP. Because RNA mimics are unstable after in vivo administration, we have chemically engineered miRNA 130b-3p mimic (named PS-OMe miR130) to improve its stability by protection from nuclease activity. We hypothesize that PS-OMe miR130 reduces eCIRP-mediated injury and inflammation in a murine model of hepatic ischemia/reperfusion (I/R), a model of sterile inflammation. METHODS Adult male mice underwent 70% hepatic ischemia for 60 minutes and 24-hour reperfusion. At the start of reperfusion, mice were treated intravenously with vehicle (phosphate-buffered saline) or PS-OMe miR130. Blood and liver tissue were collected after 24 hours for biochemical analysis. Apoptosis in the liver tissue was determined by transferase dUTP nick-end labeling assay. RESULTS After hepatic I/R, organ injury markers including aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase significantly decreased after PS-OMe miR130 treatment. Furthermore, histological analysis of liver sections demonstrated significantly less injury in PS-OMe miR130 treatment mice versus vehicle mice. In addition, tumor necrosis factor α mRNA, interleukin-1β mRNA, and neutrophil infiltration (myeloperoxidase activity and granulocyte receptor 1 immunohistochemistry) were significantly attenuated after PS-OMe miR130 treatment. Finally, apoptosis significantly decreased in liver tissue after treatment. CONCLUSION PS-OMe miR130 decreases eCIRP-mediated injury and inflammation in a murine model of hepatic I/R.
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